Open-label Safety Extension Study Assessing Safety and Tolerability of LAI in Patients Who Participated in Study INS-212
Primary Purpose
NTM Lung Infection Due to MAC
Status
Completed
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
LAI 590 mg
Multi-drug regimen
Sponsored by
About this trial
This is an interventional treatment trial for NTM Lung Infection Due to MAC focused on measuring ALIS, ARIKAYCE
Eligibility Criteria
Key Inclusion Criteria:
- had successfully completed the Month 6 and End of Treatment visits in Study INS-212
- had not achieved the INS-212 protocol definition of culture conversion by Month 6 in Study INS-212 OR had experienced a relapse or recurrence by Month 6 in Study INS-212.
Key Exclusion Criteria:
1. achieved culture conversion without relapse or recurrence in the Study INS-212 study by Month 6
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Prior LAI + Multidrug Regimen
Prior Multidrug Regimen Alone
Arm Description
Participants in the prior Study INS-212 who received LAI+MDR. All participants in this safety extension study received LAI+MDR.
Participants in the prior Study INS-212 who received MDR alone. All participants in this safety extension study received LAI+MDR.
Outcomes
Primary Outcome Measures
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
TEAEs are defined as those AEs that occurred on or after the date of first dose of study medication in INS-312 and within 28 days after the last dose. If it couldn't be determined whether the AE is treatment emergent due to a partial onset date, then it was classified as treatment emergent.
Secondary Outcome Measures
Number of Participants Achieving Culture Conversion by Month 6 and Month 12
6 months: Converters are defined as participants who had 3 consecutive monthly MAC-negative sputum cultures by Month 6 (last opportunity to convert was at Month 4).
12 months: Converters are defined as participants who had 3 consecutive monthly MAC-negative sputum cultures by Month 12 (last opportunity to convert was at Month 10).
Time to Culture Conversion
The time to culture conversion is defined as the date of conversion for participants achieving culture conversion is defined as the date of the first of 3-consecutive monthly negative sputum cultures. Then, the number of days to culture conversion is defined as the difference between the date of conversion and the date of first dose of LAI.
Change From Baseline (Day 1) to Month 6 and Month 12 in the 6MWT Distance
A 6-minute walk assessment of exertional capability was performed at Baseline (Day 1) and Month 6 and Month 12/EOT. The standardized protocol based on the American Thoracic Society (ATS) guidelines (http://doi.org/10.1164/ajrccm.166.1.at1102) was used. After assessments were performed for heart rate, blood pressure, pulse oximetry (SpO2), dyspnea, and overall fatigue using the Borg scale, participants were instructed to walk on a prescribed course as far as they could in 6 minutes. Pre-test assessment parameters were repeated after exertion. The maximum distance achieved and post exertion heart rate and SpO2 were compared to pre-test values. The maximum distance achieved was recorded in the electronic case report form.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02628600
Brief Title
Open-label Safety Extension Study Assessing Safety and Tolerability of LAI in Patients Who Participated in Study INS-212
Official Title
An Open-Label Safety Extension Study to a Multicenter Study of Liposomal Amikacin for Inhalation (LAI) in Adult Patients With Nontuberculous Mycobacterial (NTM) Lung Infections Caused by Mycobacterium Avium Complex (MAC) That Are Refractory to Treatment
Study Type
Interventional
2. Study Status
Record Verification Date
January 2020
Overall Recruitment Status
Completed
Study Start Date
February 5, 2016 (Actual)
Primary Completion Date
October 17, 2018 (Actual)
Study Completion Date
October 17, 2018 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Insmed Incorporated
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
This is an open-label safety extension study to assess the safety and tolerability of once daily dosing of 590 mg Liposomal Amikacin for Inhalation (LAI) added to a multi-drug regimen in participants with nontuberculous mycobacterial (NTM) lung infections due to Mycobacterium avium complex (MAC) who were refractory to therapy and failed to convert in Study INS-212 (NCT02344004).
Detailed Description
Safety and tolerability of once daily dosing of 590 mg Liposomal Amikacin for Inhalation (LAI) added to a multi-drug regimen in participants with non-tuberculous mycobacterium (NTM) lung infections due to Mycobacterium avium complex (MAC) who are refractory to therapy and failed to convert in Study INS-212.
Participants participating in Study INS-212 who had not achieved the INS-212 protocol definition of culture conversion (3 consecutive monthly negative sputum cultures) or who had experienced a relapse or recurrence (agar positive or more than 2 consecutive broth positive results after culture conversion had occurred) by Month 6, as determined by their sputum culture results from Day 1 through Month 6 and confirmed at their scheduled Month 8 visit, were eligible to participate in Study INS-312. For participants who chose to participate in Study INS-312, the Month 8 visit of Study INS-212 became their end of treatment (EOT) visit; these participants were then asked to provide written informed consent for Study INS-312 and were enrolled directly into Study INS-312 after having met all eligibility criteria.
Participants in Study INS-212 had either received 590 mg LAI plus an MDR (LAI + MDR arm) or a multidrug regimen alone (MDR alone arm). All participants in this safety extension study were to continue the multidrug antimycobacterial regimen that they were receiving during Study INS-212 and will receive LAI 590 mg administered daily (QD) for up to 12 months. The participants will remain in the study for up to a total of 13 months (up to 12 months on-treatment plus 1 month off LAI treatment for safety follow up).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
NTM Lung Infection Due to MAC
Keywords
ALIS, ARIKAYCE
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
163 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Prior LAI + Multidrug Regimen
Arm Type
Experimental
Arm Description
Participants in the prior Study INS-212 who received LAI+MDR. All participants in this safety extension study received LAI+MDR.
Arm Title
Prior Multidrug Regimen Alone
Arm Type
Experimental
Arm Description
Participants in the prior Study INS-212 who received MDR alone. All participants in this safety extension study received LAI+MDR.
Intervention Type
Drug
Intervention Name(s)
LAI 590 mg
Other Intervention Name(s)
Amikacin Liposome Inhalation Suspension (ALIS), ARIKAYCE®
Intervention Description
LAI 590 mg QD: administered by inhaling drug product that had been aerosolized in an investigational eFlow nebulizer over approximately 14 minutes
Intervention Type
Drug
Intervention Name(s)
Multi-drug regimen
Intervention Description
Multidrug antimycobacterial regimen from study INS-212
Primary Outcome Measure Information:
Title
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
Description
TEAEs are defined as those AEs that occurred on or after the date of first dose of study medication in INS-312 and within 28 days after the last dose. If it couldn't be determined whether the AE is treatment emergent due to a partial onset date, then it was classified as treatment emergent.
Time Frame
From baseline to 28 days after end of treatment, up to 13 months
Secondary Outcome Measure Information:
Title
Number of Participants Achieving Culture Conversion by Month 6 and Month 12
Description
6 months: Converters are defined as participants who had 3 consecutive monthly MAC-negative sputum cultures by Month 6 (last opportunity to convert was at Month 4).
12 months: Converters are defined as participants who had 3 consecutive monthly MAC-negative sputum cultures by Month 12 (last opportunity to convert was at Month 10).
Time Frame
by Month 6 and Month 12
Title
Time to Culture Conversion
Description
The time to culture conversion is defined as the date of conversion for participants achieving culture conversion is defined as the date of the first of 3-consecutive monthly negative sputum cultures. Then, the number of days to culture conversion is defined as the difference between the date of conversion and the date of first dose of LAI.
Time Frame
by Month 12
Title
Change From Baseline (Day 1) to Month 6 and Month 12 in the 6MWT Distance
Description
A 6-minute walk assessment of exertional capability was performed at Baseline (Day 1) and Month 6 and Month 12/EOT. The standardized protocol based on the American Thoracic Society (ATS) guidelines (http://doi.org/10.1164/ajrccm.166.1.at1102) was used. After assessments were performed for heart rate, blood pressure, pulse oximetry (SpO2), dyspnea, and overall fatigue using the Borg scale, participants were instructed to walk on a prescribed course as far as they could in 6 minutes. Pre-test assessment parameters were repeated after exertion. The maximum distance achieved and post exertion heart rate and SpO2 were compared to pre-test values. The maximum distance achieved was recorded in the electronic case report form.
Time Frame
From baseline to Month 12 or end of treatment
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Key Inclusion Criteria:
had successfully completed the Month 6 and End of Treatment visits in Study INS-212
had not achieved the INS-212 protocol definition of culture conversion by Month 6 in Study INS-212 OR had experienced a relapse or recurrence by Month 6 in Study INS-212.
Key Exclusion Criteria:
1. achieved culture conversion without relapse or recurrence in the Study INS-212 study by Month 6
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Kevin Mange, MD
Organizational Affiliation
Insmed Incorporated
Official's Role
Study Director
12. IPD Sharing Statement
Citations:
PubMed Identifier
33326356
Citation
Winthrop KL, Flume PA, Thomson R, Mange KC, Yuen DW, Ciesielska M, Morimoto K, Ruoss SJ, Codecasa LR, Yim JJ, Marras TK, van Ingen J, Wallace RJ Jr, Brown-Elliott BA, Coulter C, Griffith DE. Amikacin Liposome Inhalation Suspension for Mycobacterium avium Complex Lung Disease: A 12-Month Open-Label Extension Clinical Trial. Ann Am Thorac Soc. 2021 Jul;18(7):1147-1157. doi: 10.1513/AnnalsATS.202008-925OC.
Results Reference
derived
Learn more about this trial
Open-label Safety Extension Study Assessing Safety and Tolerability of LAI in Patients Who Participated in Study INS-212
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